1. Field of the Invention
The present invention relates to a process for producing an optically active .gamma.-hydroxy-L-glutamic acid, that is, threo-.gamma.-hydroxy-L-glutamic acid [(2S,4S)-4-hydroxyglutamic acid] or erythro-.gamma.-hydroxy-L-glutamic acid [(2S,4R)-4-hydroxyglutamic acid].
An optically active .gamma.-hydroxy-L-glutamic acid is known to have activity of inhibiting glutamine synthetase [Khim-Farm. Zh., 18, 655 (1984)] or incorporation of glutamic acid by presynaptic vesicle [Neurochem. Res., 18, 79 (1993)], and it is useful as a reagent for investigation of the above-mentioned enzyme or organ. Further, this acid is useful as a medicament based on the above-mentioned activity.
2. Prior Art
As a conventional method for producing an optically active .gamma.-hydroxy-L-glutamic acid, known are a method in which the optically active .gamma.-glutamic acid is separated from a mixture of four kinds of isomers of .gamma.-hydroxyglutamic acid which is chemically synthesized from ethyl-.alpha.-acetoxy-.beta.-chloropropionic acid and ethylacetamidocyanic acid, a method in which the optically active .gamma.-glutamic acid is separated from a mixture of threo- and erythro-.gamma.-hydroxy-L-glutamic acids formed by reacting DL-4-hydroxy-2-ketoglutaric acid and ammonia with glutamic acid dehydrogenase derived from mammal liver in the presence of NADPH [Biochem. Biophis. Acta., 77, 133 (1963)], a method in which threo-.gamma.-hydroxy-L-glutamic acid [(2S,4S)-4-hydroxyglutamic acid] is extracted from Phlox decussata (Methods in Enzymology, 17, part B, 277), a method in which L-4-hydroxy-2-ketoglutaric acid reacts with cisteinesulfinic acid in the presence of transaminase to form threo-.gamma.-hydroxy-L-glutamic acid [Tetrahedron Lett., 28, 1277 (1987)], and a method in which the optically active .gamma.-glutamic acid is formed by reacting .DELTA..sup.1 -pyrroline-3-hydroxy-5-carboxylate with .DELTA..sup.1 -pyrroline dehydrogenase derived from bovine liver [J. Biochem., 235, 3504 (1960)].
The conventional methods for producing an optically active .gamma.-hydroxy-L-glutamic acid involve the following defects.
(1) The starting materials are expensive.
(2) A step of separating isomers is required and the cost is high.
(3) A yield is low.
Accordingly, the development of a method for producing the optically active .gamma.-hydroxy-L-glutamic acid advantageously on an industrial scale has been in demand.